The production of protein which occurs in a normal cell becomes altered at the onset of cancer. This alteration of protein synthesis may be caused by a change in one or more of the components of the cell's protein synthesizing machinery. A class of major components involved in protein production, transfer ribonucleic acid (tRNA) molecules, have been shown to participate in the regulation of protein synthesis. Therefore, the altered protein biosynthesis which is concomitant with neoplasia may mean a change in the functioning of one or more tRNA molecules, the synthesis of modified or completely new tRNA molecules or a relative increase in the synthesis of particular tRNAs. We have begun to develop methods for the radioactive labeling, fractionation, and characterization of specific human tRNA molecules. These methods will be used in a variety of investigations all of which will probe the biochemical genetics of tRNA from normal and neoplastic human cells. Using as broad a spectrum of normal and leukemic human lymphocytes as feasibly possible, we wish to compare the modified nucleotides and nucleotide sequences of specific tRNA molecules from normal human lymphocytes with that of lymphocytes from leukemic patients during the tenure of their treatment and study the genetics of tRNA in lymphocytes by the techniques of human-mouse somatic cell hybridizations. Because tRNA participates in the regulation of protein synthesis the biochemical genetics of tRNA in leukemia and other cancers is important to our understanding of the irregular mechanisms by which protein synthesis becomes altered at the onset of these diseases.